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Clinical Heterogeneity Associated with MYO7A Variants Relies on Affected Domains
Autosomal dominant hearing loss (ADHL) manifests as an adult-onset disease or a progressive disease. MYO7A variants are associated with DFNA11, a subtype of ADHL. Here, we examined the role and genotype–phenotype correlation of MYO7A in ADHL. Enrolled families suspected of having post-lingual sensor...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9028242/ https://www.ncbi.nlm.nih.gov/pubmed/35453549 http://dx.doi.org/10.3390/biomedicines10040798 |
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author | Joo, Sun Young Na, Gina Kim, Jung Ah Yoo, Jee Eun Kim, Da Hye Kim, Se Jin Jang, Seung Hyun Yu, Seyoung Kim, Hye-Youn Choi, Jae Young Gee, Heon Yung Jung, Jinsei |
author_facet | Joo, Sun Young Na, Gina Kim, Jung Ah Yoo, Jee Eun Kim, Da Hye Kim, Se Jin Jang, Seung Hyun Yu, Seyoung Kim, Hye-Youn Choi, Jae Young Gee, Heon Yung Jung, Jinsei |
author_sort | Joo, Sun Young |
collection | PubMed |
description | Autosomal dominant hearing loss (ADHL) manifests as an adult-onset disease or a progressive disease. MYO7A variants are associated with DFNA11, a subtype of ADHL. Here, we examined the role and genotype–phenotype correlation of MYO7A in ADHL. Enrolled families suspected of having post-lingual sensorineural hearing loss were selected for exome sequencing. Mutational alleles in MYO7A were identified according to ACMG guidelines. Segregation analysis was performed to examine whether pathogenic variants segregated with affected status of families. All identified pathogenic variants were evaluated for a phenotype–genotype correlation. MYO7A variants were detected in 4.7% of post-lingual families, and 12 of 14 families were multiplex. Five potentially pathogenic missense variants were identified. Fourteen variants causing autosomal dominant deafness were clustered in motor and MyTH4 domains of MYO7A protein. Missense variants in the motor domain caused late onset of hearing loss with ascending tendency. A severe audiological phenotype was apparent in individuals carrying tail domain variants. We report two new pathogenic variants responsible for DFNA11 in the Korean ADHL population. Dominant pathogenic variants of MYO7A occur frequently in motor and MyTH4 domains. Audiological differences among individuals correspond to specific domains which contain the variants. Therefore, appropriate rehabilitation is needed, particularly for patients with late-onset familial hearing loss. |
format | Online Article Text |
id | pubmed-9028242 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-90282422022-04-23 Clinical Heterogeneity Associated with MYO7A Variants Relies on Affected Domains Joo, Sun Young Na, Gina Kim, Jung Ah Yoo, Jee Eun Kim, Da Hye Kim, Se Jin Jang, Seung Hyun Yu, Seyoung Kim, Hye-Youn Choi, Jae Young Gee, Heon Yung Jung, Jinsei Biomedicines Article Autosomal dominant hearing loss (ADHL) manifests as an adult-onset disease or a progressive disease. MYO7A variants are associated with DFNA11, a subtype of ADHL. Here, we examined the role and genotype–phenotype correlation of MYO7A in ADHL. Enrolled families suspected of having post-lingual sensorineural hearing loss were selected for exome sequencing. Mutational alleles in MYO7A were identified according to ACMG guidelines. Segregation analysis was performed to examine whether pathogenic variants segregated with affected status of families. All identified pathogenic variants were evaluated for a phenotype–genotype correlation. MYO7A variants were detected in 4.7% of post-lingual families, and 12 of 14 families were multiplex. Five potentially pathogenic missense variants were identified. Fourteen variants causing autosomal dominant deafness were clustered in motor and MyTH4 domains of MYO7A protein. Missense variants in the motor domain caused late onset of hearing loss with ascending tendency. A severe audiological phenotype was apparent in individuals carrying tail domain variants. We report two new pathogenic variants responsible for DFNA11 in the Korean ADHL population. Dominant pathogenic variants of MYO7A occur frequently in motor and MyTH4 domains. Audiological differences among individuals correspond to specific domains which contain the variants. Therefore, appropriate rehabilitation is needed, particularly for patients with late-onset familial hearing loss. MDPI 2022-03-29 /pmc/articles/PMC9028242/ /pubmed/35453549 http://dx.doi.org/10.3390/biomedicines10040798 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Joo, Sun Young Na, Gina Kim, Jung Ah Yoo, Jee Eun Kim, Da Hye Kim, Se Jin Jang, Seung Hyun Yu, Seyoung Kim, Hye-Youn Choi, Jae Young Gee, Heon Yung Jung, Jinsei Clinical Heterogeneity Associated with MYO7A Variants Relies on Affected Domains |
title | Clinical Heterogeneity Associated with MYO7A Variants Relies on Affected Domains |
title_full | Clinical Heterogeneity Associated with MYO7A Variants Relies on Affected Domains |
title_fullStr | Clinical Heterogeneity Associated with MYO7A Variants Relies on Affected Domains |
title_full_unstemmed | Clinical Heterogeneity Associated with MYO7A Variants Relies on Affected Domains |
title_short | Clinical Heterogeneity Associated with MYO7A Variants Relies on Affected Domains |
title_sort | clinical heterogeneity associated with myo7a variants relies on affected domains |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9028242/ https://www.ncbi.nlm.nih.gov/pubmed/35453549 http://dx.doi.org/10.3390/biomedicines10040798 |
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